Friday, June 23, 2017

Hepatitis C: AbbVies MAVIRET (glecaprevir/pibrentasvir) and Gilead’s Vosevi (Sofosbuvir/Velpatasvir/Voxilaprevir) Receives CHMP Positive Opinion

AbbVies  MAVIRET (glecaprevir/pibrentasvir) and Gilead’s Vosevi (Sofosbuvir/Velpatasvir/Voxilaprevir) Receives CHMP Positive Opinion

Two new medicines recommended for the treatment of chronic hepatitis C

Maviret and Vosevi evaluated under accelerated assessment

The European Medicines Agency has recommended granting marketing authorisations in the European Union (EU) for Maviret and Vosevi, two new medicines indicated for the treatment of chronic hepatitis C virus (HCV) infection in adults.

HCV infection is a major public health challenge. It affects between 0.4% and 3.5% of the population in different EU Member States and is the most common single cause of liver transplantation in the EU. Approximately 15 million people are chronically infected with HCV throughout Europe.

Both Maviret and Vosevi are active against all genotypes of the virus and, with some differences between the two medicines, may be specifically useful in some patients who failed or cannot use previously available therapies. As this is considered to be of major public health interest in terms of therapeutic innovation, both medicines were evaluated under the EU’s accelerated assessment mechanism, which aims to speed up patients’ access to new medicines where there is an unmet medical need.

Maviret and Vosevi belong to the direct acting antivirals against HCVs which have reshaped the way chronic HCV infection is treated. By blocking the action of proteins essential for HCV replication, this type of medicine achieves high cure rates of the infection and does not require the concomitant use of interferons, medicines which are associated with poor tolerability and potentially serious side effects.

Despite the rapid development of new therapies there is still a need for a range of alternative treatment options to serve the different medical needs of the millions of people suffering from the disease. The more treatment options that are available, the better chance a patient has to get the right treatment to cure the disease and to lead a longer and healthier life.

Maviret and Vosevi are the first medicines for which accelerated assessment has been carried out within 120 days, after a recent review of the timetable for this mechanism.

Maviret contains two next generation direct-acting and antiviral agents: glecaprevir, an inhibitor of HCV NS3/4A protease, and pibrentasvir, an inhibitor of HCV NS5A. Both components are pangenotypic.

The effects of Maviret were studied in a total of 2,376 patients who participated in eight pivotal and three supportive clinical trials. The hepatitis C virus could no longer be detected in over 90% of patients 12 weeks after the end of treatment. If the blood of patients is clear of hepatitis C virus for more than 12 weeks they are generally considered as being cured of the infection. Adverse events reported with Maviret were generally mild, including headache, fatigue, diarrhoea, nausea and abdominal pain.

The applicant for Maviret received scientific advice from the Agency during the development of the medicine.

Vosevi is composed of sofosbuvir (a nucleotide analogue non-structural protein NS5B polymerase inhibitor), velpatasvir (an HCV NS5A inhibitor), which were previously approved in other medicinal product, to which is added voxilaprevir (a novel pangenotypic HCV NS3/4A protease inhibitor).

The effects of Vosevi were studied in four main clinical trials involving over 1,700 patients. Two studies were in previously untreated patients and two in patients in whom previous treatment (in some cases with an NS5A inhibitor) had not cleared the virus. Treatment was given for 12 weeks in the previously treated patients and eight weeks in the untreated. The hepatitis C virus could no longer be detected in over 90% of patients 12 weeks after the end of treatment with Vosevi. Mild nausea, headache and diarrhoea were the most common side effects observed. Other potentially related adverse effects were decreased appetite, vomiting, muscle spasms and rash.

The opinions adopted by the CHMP at its June 2017 meeting are an intermediary step on Maviret's and Vosevi’s path to patient access. The CHMP opinions will now be sent to the European Commission for the adoption of decisions on EU-wide marketing authorisations through an accelerated procedure. Once a marketing authorisation has been granted, decisions about price and reimbursement will take place at the level of each Member State, taking into account the potential role/use of these medicines in the context of the national health system of that country.

The applicant for Maviret is AbbVie Ltd.
The applicant for Vosevi is Gilead Sciences International Ltd.

Press Release
European CHMP Adopts Positive Opinion for Gilead’s Vosevi® (Sofosbuvir/Velpatasvir/Voxilaprevir) for the Treatment of All Chronic Hepatitis C Genotypes
– Vosevi is Gilead’s Fourth Sofosbuvir-Based Treatment to Receive CHMP Positive Opinion for the Treatment of Chronic HCV Infection –
FOSTER CITY, Calif.--(BUSINESS WIRE)--Jun. 23, 2017-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the Committee for Medicinal Products for Human Use (CHMP), the scientific committee of the European Medicines Agency (EMA), has adopted a positive opinion on the company’s Marketing Authorization Application (MAA) for Vosevi®, an investigational, once-daily, single tablet regimen of sofosbuvir 400 mg, velpatasvir 100 mg, and voxilaprevir 100 mg (SOF/VEL/VOX) for the treatment of chronic hepatitis C virus (HCV)-infected patients. The data included in the application support the use of SOF/VEL/VOX in patients with and without compensated cirrhosis, with all genotypes (GT1-6) of HCV infection regardless of prior therapy, including 8 weeks of treatment for HCV direct-acting antiviral (DAA)-naïve patients without cirrhosis, as well as 12 weeks of treatment for patients who have previously failed therapy with a DAA-containing regimen.
The CHMP positive opinion was adopted following an accelerated assessment procedure, reserved for medicinal products expected to be of major public health interest. The recommendation will now be reviewed by the European Commission, which has the authority to approve medicines for use in the 28 countries of the European Union, Norway and Iceland.
The MAA for SOF/VEL/VOX is supported by data from four Phase 3 studies. Two studies (POLARIS-1 and POLARIS-4), evaluated 12 weeks of the single tablet regimen in patients with genotypes 1-6 HCV infection previously treated unsuccessfully with DAA-containing regimens, including NS5A inhibitors. Two other studies (POLARIS-2 and POLARIS-3) evaluated 8 weeks of SOF/VEL/VOX in DAA-naïve patients with genotypes 1-6 HCV infection. Across POLARIS-1 and POLARIS-4, 97 percent of patients treated with SOF/VEL/VOX (n=431/445) achieved the primary efficacy endpoint of SVR12. In POLARIS-2, 95 percent of patients with genotypes 1-6 HCV infection with and without cirrhosis treated with SOF/VEL/VOX (n=477/501) achieved the primary efficacy endpoint of SVR12. In POLARIS-3, 96 percent of patients with genotype 3 infection and cirrhosis treated with SOF/VEL/VOX (n=106/110) achieved the primary efficacy endpoint of SVR12. The most common adverse events among patients who received SOF/VEL/VOX in the POLARIS studies were headache, fatigue, diarrhea and nausea.
Sofosbuvir as a single agent was granted marketing authorization in the European Union on January 16, 2014, under the trade name Sovaldi®, for use in combination with other agents. The single tablet regimen of sofosbuvir (400 mg) and ledipasvir (90 mg) received marketing authorization in the European Union on November 18, 2014, under the trade name Harvoni®. The single tablet regimen of sofosbuvir (400 mg) and velpatasvir (100 mg) received marketing authorization in the European Union on July 8, 2016, under the trade name Epclusa®.
Gilead has also submitted a regulatory application for SOF/VEL/VOX in the United States. Gilead filed the New Drug Application for SOF/VEL/VOX on December 8, 2016, and the Food and Drug Administration (FDA) has set a target action date under the Prescription Drug User Fee Act of August 8, 2017.
SOF/VEL/VOX is an investigational product and its safety and efficacy has not been established and is not approved anywhere globally.

Press Release
AbbVie Receives CHMP Positive Opinion for MAVIRET™ (glecaprevir/pibrentasvir) for the Treatment of Chronic Hepatitis C in All Major Genotypes (GT1-6)
- If approved, MAVIRET™ will provide a shorter, 8-week, pan-genotypic (GT1-6), once-daily option for the majority of people living with the hepatitis C virus (HCV)(1)*
- MAVIRET would also be an additional HCV treatment option for patients with specific treatment challenges, such as those with compensated cirrhosis, chronic kidney disease and genotype 3
- Final European Commission decision expected Q3 2017

NORTH CHICAGO, Ill., June 23, 2017 /PRNewswire/ -- AbbVie ABBV 0.32%, a global biopharmaceutical company, today announced that the European Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has granted a positive opinion recommending marketing authorization of MAVIRET™ (glecaprevir/pibrentasvir), an investigational, pan-genotypic treatment for adults with chronic hepatitis C virus (HCV) infection. If approved, MAVIRET will be a once-daily, ribavirin-free, 8-week option for patients without cirrhosis and who are new to treatment across all genotypes (GT1-6), who comprise the majority of people living with HCV.1 The European Commission will now review the CHMP opinion and a final decision is expected in Q3 2017.

"MAVIRET represents a new generation of HCV therapy and has the potential to be a shorter, 8-week option for patients living with this serious, chronic illness," said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie. "Today's CHMP positive opinion takes us closer to delivering on AbbVie's mission to address continued unmet needs by bringing a new pan-genotypic option to people living with HCV in Europe."

The CHMP positive opinion is supported by 97.5 percent (n=807/828) SVR12 rates with 8 weeks of MAVIRET across GT1-6 chronic HCV infected patients without cirrhosis and who are new to treatment, with varied patient and viral characteristics.2 In an integrated analysis (n=2,265), less than 0.4 percent of patients discontinued treatment.3 The reported adverse reactions (incidence greater than or equal to 10 percent) were headache and fatigue.3 The type and severity of adverse reactions in patients with cirrhosis were overall comparable to those seen in patients without cirrhosis.3

"While the HCV treatment landscape has transformed significantly over recent years, the disease continues to be a global public health problem and treatment challenges remain," said Stefan Zeuzem, M.D., chief of the department of medicine at the J.W. Goethe University Hospital in Frankfurt, Germany. "In clinical studies, MAVIRET demonstrated high SVR rates across all genotypes of HCV patients (GT1-6). If approved, MAVIRET would remove many of the complexities of pre-treatment patient evaluation and has the potential to help facilitate the care and management of HCV."

MAVIRET is also intended to be an additional option for patients with specific treatment challenges. This includes chronic HCV patients with compensated cirrhosis (Child-Pugh A), and those who currently have limited treatment options, such as patients with severe chronic kidney disease, including those on dialysis, and patients infected with genotype 3.

The marketing authorization application (MAA) for MAVIRET is under an accelerated assessment by the EMA, which is granted to new medicines of major public health interest. The MAA evaluation is conducted under the centralized licensing procedure, and if approved, will result in a marketing authorization valid in all 28 member states of the European Union, as well as Iceland, Liechtenstein and Norway. AbbVie's investigational, pan-genotypic regimen has also been granted accelerated review designations by other regulatory authorities including the U.S. Food and Drug Administration and Japanese Ministry of Health, Labour and Welfare. MAVIRET is an investigational regimen and its safety and efficacy have not been established. 

About MAVIRET™ (glecaprevir/pibrentasvir)
AbbVie's MAVIRET™ (glecaprevir/pibrentasvir) clinical development program was designed to investigate a pan-genotypic, once-daily, ribavirin-free treatment with the potential to provide a faster path to virologic cure** for all major HCV genotypes (GT1-6) and with the goal of addressing specific treatment challenges, including compensated cirrhosis (Child-Pugh A), chronic kidney disease and genotype 3. MAVIRET is being evaluated as a potential 8-week, pan-genotypic treatment for the majority of people living with HCV,1 those without cirrhosis and who are new to treatment,* and regardless of viral and patient characteristics.

MAVIRET is a fixed-dose combination of two distinct antiviral agents: glecaprevir (100mg), an NS3/4A protease inhibitor, and pibrentasvir (40mg), an NS5A inhibitor, dosed once-daily as three oral tablets.

Glecaprevir was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals ENTA 1.16% for HCV protease inhibitors and regimens that include protease inhibitors.

*Patients who are treatment-naive or had prior treatment experience with IFN-based treatments ([peg]IFN +/- RBV or SOF/RBV +/- pegIFN).
**Patients who achieve a sustained virologic response at 12 weeks post treatment (SVR12) are considered cured of hepatitis C.

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